Acute Kidney Injury Part I Fall 2024 Lecture Notes PDF

PBSN: 529- Pharmacology & Medicinal Chemistry II ACUTE KIDNEY INJURY PART- I Fall 2024 Time: Tue: 2:00 to 4:15 PM/ Thur: 10:15 to 12:30 PM 1  LECTURE SPECIFIC OBJECTIVES * Describe Electr...

PBSN: 529- Pharmacology & Medicinal Chemistry II ACUTE KIDNEY INJURY PART- I Fall 2024 Time: Tue: 2:00 to 4:15 PM/ Thur: 10:15 to 12:30 PM 1  LECTURE SPECIFIC OBJECTIVES * Describe Electrolyte imbalances in the body and its consequences; * Explain pathophysiology of Kidney diseases (AKI/ARF & CKI); * List factors that cause AKI (ARF) and classify ARF; * Identify medication-related causes of the various types of acute kidney injury * Explain various forms of ARF; * List definitions and classification of AKI; * Describe the epidemiology and clinical outcome of AKI; * Describe complications associated with acute kidney injury * Describe etiology and diagnosis of AKI; * Explain approach and management of AKI; * Describe risk factors and preventive strategies of AKI; 2 ( see lecture a for notes on this slide > - all metals are nephrotoxic , S ANTIBIOTICS hypertension Leg aminoglycosides). HPI= History of the Present illness; PMH= Past Medical History; Hemolytic uremic syndrome (HUS); Thrombotic thrombocytopenic purpura (TTP); BPH- Benign Prostatic Hyperplasia; Third place losses: Accumulation of fluid from the blood within body cavities, intestinal areas, or areas of the body that normally contain little fluid. Acute Kidney Injury (AKI) – Definitions and Risk Factors * Abrupt decline in renal function resulting in inability to properly excrete waste (BUN & Cr) and maintain acid-base balance; > critical ; alkalosis & acidosis are FATAL * An acute decrease in kidney function or glomerular filtration rate (GFR) over hours, days, or even weeks and associated with an accumulation of waste products and (usually) volume; * Renal insufficiency + abnormal biochemical values and altered homeostasis; (i) Fluid overload; (ii) Acid-base abnormalities; (iii) Increased SCr and/or BUN Misc. clinical definitions of this disease: (i) A decrease of 25% or greater in estimated GFR (eGFR); (ii) An increase in SCr of 0.5 mg/dL or greater; (for healthy individuals (iii) An increase of 1 mg/dL or more in SCr in patients with CKD; (iv) Urine output 50 mL but less than 500 mL/day * Non-Oliguria – Urine output greater than 500 mL/day (better outcomes) * Normal Urine output – 1 mL/kg/hour 5 MEMORIZE Which of the following criteria is required within Diagnostic criteria: As per ‘The Acute Kidney a 48-hour period in order to diagnose AKI as per ‘The Acute Kidney Injury Network (AKIN)’: ? Injury Network (AKIN)’: one of the following within a 48-hour period is required- ✓A. An absolute increase in Scr of more than 0.3 mg/dL (i) An absolute increase in Scr of more than 0.3 mg/dL ✓B. An increase in baseline SCr by 50% or more (ii) An increase in baseline SCr by 50% or more ✓C. Urine output of less than 0.5 mL/kg/hour for more than 6 hours (iii) Urine output of less than 0.5 mL/kg/hour for more than 6 hours D. Occurance of both micro & macroalbuminurea (>500 nanograms/L) (iv) Can further classify into stages 1–3 on the basis of E. Presence of beta-glucuronidase in the urine degree of SCr rise and urine output 300 units/L 6  Lend stage Kidney disease Kidney disease improving global outcomes MEMORIZE Agents Used to Treat/Prevent AKI Examples of oral thiazide diuretics include: Chlorothiazide (Diuril) Chlorthalidone Hydrochlorothiazide (Microzide) Indapamide Metolazone Examples of loop diuretics include: Bumetanide (Bumex) Ethacrynic acid (Edecrin) Furosemide (Lasix) Torsemide (Demadex) Examples of potassium-sparing diuretics include: Amiloride Eplerenone (Inspra) Spironolactone (Aldactone, Carospir) Triamterene (Dyrenium) 8  Prevention of AKI Prevention of AKI – Pharmacologic General Principles therapy * Avoid nephrotoxic agents; * Loop diuretics ~ Increase renal blood flow * Ensure adequate hydration ~ Increase urine flow - Isotonic crystalloids ~ Most useful for management of fluid overload - Isotonic normal saline for patients at risk for AKI ~ Do not use for prevention and it does not improve outcomes * Patient education; ~ compassionate * N-acetylcysteine (NAC) use * Drug therapies to decrease incidence ~ Contrast-induced nephropathy of contrast-induced nephropathy; ~ Well tolerated, little adverse effects > When patients take radio contrast agents  Goals of Therapy Treatment Options * Maintain appropriate BP * Nonpharmacologic Therapy * Monitor and manage electrolytes daily ~ Avoid nephrotoxic agents ~Target for UOP of ≥ 0.5mL/kg/hr * Eliminate or minimize insult that precipitated ~ Hydration AKI ~ Use caution with CHF, anuria, and ~ Discontinue offending agent oliguria ~ Aggressive hydration ~ Renal Replacement Therapy (RRT) – dialysis ~ Maintain renal perfusion used in 4 5 stage ~ Pharmacologic Therapy or * Expedite recovery of baseline renal function ~ Diuretics ~ Mannitol * Facilitate renal recovery and minimize injury  Pharmacologic Therapy Mannitol Loop Diuretics * MOA: Increases the osmotic pressure of * No benefit for survival outcomes glomerular filtrate which inhibits tubular reabsorption of water and electrolytes; * Furosemide is most commonly used * Equally effective * Dose ~Switching loop diuretics is unlikely to ~12.5-25 grams IV over 3-5 minutes; be effective ~ Only can be given parenterally; * Torsemide and bumetanide have greater * Induces a hyperosmolar state oral bioavailability and are more potent ~ Can cause AKI ~ Furosemide:Torsemide: 4:1 ~ Requires careful monitoring of urine ~ Furosemide:Bumetanide: 40:1 output, serum electrolytes, and osmolality  MEMORIZE (Not > a high-yield slide) ⑪ > difficult ② ③ don't ⑪ confuse nephrotic with repurITIC 7 can lead to stroke < Vital organs (e g.. heart , Kidney) don't get enough blood ③ ⑦ (e.. ACE-R g therapy > MEMORIZE contrast-induced AkI Laye injected before scan) (N-acetylcysteine) MEMORIZE Most common out of these 3 to happen & Hyperphosphatemia calcium imbalance rare; Hyperkalemia ~ Life threatening cardiac arrhythmias may occur if K+ > 6 mEq/L MEMORIZE  DIKD DRUG-INDUCED KIDENY DISEASE Primary Prevention Strategy is to avoid use of nephrotoxic agents for patients at an increased risk for toxicity 17 FYI ATN(P): ACUTE TUBULAR NECROSIS AMINOGLYCOSIDES, ANTINEOPLASTICS, ATN(D): ACUTE TUBULAR FYI NECROSIS AMPHOTERICIN, NEPHROTIC SYNDROME GLYCOLS, RADIOCONTRAST AGENTS CISPLATIN, GLYCOLS NSAIDS, PENICILLAMINE CAPTOPRIL HEROIN/COCAINE CORTEX METALS (Au, Hg) VASCULITIS AMPHETAMINES, NSAIDS, PENICILLINS,SULFONAMIDE S ----------------------------------------------------------- INNER MEDULLA ACUTE PRE-RENAL FAILURE AMPHOTERICIN, ANTIHYPERTENSIVES, ------------------------------------------------------------ DIURETICS, DOXORUBICIN, OBSTRUCTION OUTER MEDULLA NSAIDS, CYCLOSPORIN-A ACYCLOVIR, ANTICHOLINERGICS, BROMOCRIPTINE, ERGOT , MTX, ALKALOIDS, FLUOROQUINOLONE ACUTE INTERSTITIAL NEPHRITIS CHRONIC INTERSTITIAL NEPHRITIS ANALGESIC COMBINATIONS, CHINESE HERBS, ALLOPURINOL, RIFAMPIN, CYCLOSPORINE, METALS (PB, Cd, Li, Ge), METHYL- VANCOMYCIN, NSAIDS CCNU  DIKD -Tubular Epithelial Cell Damage * Acute Tubular Necrosis (ATN) ~ Damage to the tubule cells of the kidneys; ~Proximal and distal tubules ~Most common cause of AKI * Can be caused by: ~Aminoglycosides ~Radiocontrast media ~Amphotericin B * Osmosis Nephrosis ~ Swelling of the renal proximal tubular cells associated with glomerular filtration of sugars and dextrose; ~ Mannitol  Contrast Media-Induced Nephrotoxicity Ethiodol, Lipiodol, Diatrizoate, Iothalamate, Gadodiamide, Gadobutrol, Perflutren * Mechanism: Any combination of direct tubular toxicity, renal ischemia, and tubular obstruction; * Incidence: ~ 7-15% of patients receiving iodinated contrast ~ 50% in patients with chronic kidney disease * Clinical Presentation ~ Onset within 24-48 hours of administration ~ Scr peaks 3-4 days after exposure and returns to baseline after 7- 10 days ~ Nonoliguria ~ Irreversible AKI requiring dialysis has been reported  Contrast Media-InducedNephrotoxicity……..contd…… Ethiodol, Lipiodol, Diatrizoate, Iothalamate, Gadodiamide, Gadobutrol, Perflutren > MEMORIZE * Mechanism: Any combination of direct tubular toxicity, renal ischemia, and tubular obstruction; * Incidence: ~ 7-15% of patients receiving iodinated contrast ~ 50% in patients with chronic kidney disease * Clinical Presentation ~ Onset within 24-48 hours of administration ~ Scr peaks 3-4 days after exposure and returns to baseline after 7- 10 days ~ Nonoliguria ~ Irreversible AKI requiring dialysis has been reported  DIAGNOSIS OF RENAL DYSFUNCTIONS 22  MEMORIZE (kidney Injury Molecule 1) (neutrophil genatinase- associated (best use at late AKI-early CKD Stage lipocalin)  - Dipstick Normal Constitutes of Urine not quantitative (unless you do additional biochemical - tests) - Normally , wine should be STERILE > separate dipstick  Heads up: Chronic Kidney Disease (CKD) [This will be taught in CKD Lecture] * Progressive and irreversible loss of nephrons * Clinical manifestations seen when >75% of nephrons lost * Initial compensation by remaining nephrons, which enlarge and increase clearance capacity (compensating proliferation + hypertrophy to * Over several years, increased workload in these nephrons may cause glomerular damage, and absorb extra shock) further decline in kidney function Stage % Nephron Loss Clinical Presentation Decreased renal reserve (95%) Azotemia/uremia, fluid and [ESRD] electrolyte abnormalities - Dialysis/transplantation Clinical Manifestations OF CKD (Next Lecture series) - know functions for D > and D3 ↳ def. presence of wrea in the blood  4. Which of the following is NOT a cause of 1. Which of the following is NOT an indicator for pre-renal AKI? decreased renal function: a. Hypovolemia a. Elevated blood urea nitrogen (BUN) b. Toxicity from NSAIDs or ACE inhibitors b. Decreased blood creatinine c. Congestive heart failure c. Hyperkalemia d. Tubular necrosis d. Metabolic acidosis e. Hyponatremia 5. A high urine specific gravity suggests which type of AKI? 2. What is the major cause of acute tubular a. Pre-renal necrosis (ATN) other than ischemic injury? b. Intrinsic a. Medications c. Post-renal b. Hypertension d. Pseudorenal c. Systemic lupus erythematosus d. Vasculitis 6. What drives filtration in the nephron? a. Glomerular capillaries pressure 3. What is the best treatment for patients with ATN? b. hydrostatic pressure in the Bowman’s a. Supportive care space b. IV Furosemide c. osmotic pressure due to blood proteins c. Dopamine d. None of the above Which of the following is false? [select all that apply] ✓A. Renal blood flow = Blood flowing through the kidneys per minute = 1276 ml/min; ✓B. Renal plasma flow = Plasma flowing through kidneys per minute ≈ 1276 mL X 0.55 ≈701.8 mL plasma/min; ✓C. Flitration fraction: The % of plasma removed as filtrate by the Bowman’s capsule ≈29%; ✓D. Glomerular filtration rate (GFR): Amount of filtrate formed by kidneys per minute, by plasma flowing through Bowman’s capsuleè ≈701.8 mL plasma/min X 0.29 ≈203.5 mL/min; E. GFR can be measured by injecting inulin, and subsequently measuring the rate of urine output, the concentration of inulin in urine, and the concentration in the blood; F. In clinical practice, GFR is more often estimated from creatinine excretion, which has a small but acceptable error of measurement. Creatinine has a renal clearance of 140 mL/min; Q. A potential reason for a more rapid progression of renal failure than predicted would be: A. Drug-related effects B. poorly maintained hypertension C. volume depletion D. only a and b above E. a, b & c above Q. Which class of antihypertensive agents have been shown in several studies to decrease the progression of renal failure in non-diabetic patients? A. Alpha1-blockers B. ACE inhibitors C. Beta-blockers D. Loop- diuretics E. Calcium channel blockers 29 Q. GFR is defined as the amount of filtrate formed by kidneys per minute, via plasma flowing through Bowman’s capsule, which equals to 125 ml/min. This turns out to about __??__Litres of filtrate formed/day? A. 18L B. 180L C. 1800L D. None of the above Q. Electrolyte disturbances (disorders) can result from AKI, chronic renal failure or from drugs used to modify renal function. Therefore, electrolyte balance is key to optimal renal function. Based on the known lab values identify all the correct electrolyte concentrations and corresponding values from the following combinations: A. Hyponatremia -- Na+ 145 mEq/L mmol/L C. Hypocalcemia -- 10.5 mg/dl E. Hypophosphatemia -- 6.5 mg/dl G. Hypokalemia -- 6.5 mEq/L 30 Furosemide, Torsemide and ethacrynic acid act at which of the following segment of the Thick ascending limb of loop of Henle nephron? profoundly impacts regulation of Na+, K+, Cl-, Mg+ and Ca2+. This target of nephron A. PCT can be influenced by which of the following B. DCT drugs? C. Thin - ascending limb D. Thick - ascending limb E. Thin - descending limb A. Adenosine F. Thick - descending limb B. loop diuretics C. Osmotic agents D. ADH antagonists Which of the following can cause E. Only A &B Contrast Media- Induced Nephropathy? F. A to C all of them ✓A. Ethiodol ✓B. Lipiodol ✓C. Diatrizoate ✓D. Iothalamate E. Butanol F. Propanolol 31